In the quest to replace failed or injured body parts, fabricating them out of one of the most durable materials in the body – elastin – makes a lot of sense. Today, Dr. Ken Gregory, director of the Oregon Medical Laser Center at Providence St. Vincent Medical Center in Portland, OR, is using the material to engineer all kinds of quasi-natural structures: blood vessels, patches for internal injuries, replacement ear drums, bladders, and more.
Elastin is one of the essential proteins that hold the human body together. As the name implies, its elasticity allows body structures such as skin, blood vessels, and lungs to expand and contract. And it doesn’t break down – the elastin you’re born with lasts a lifetime. Furthermore, elastin is biocompatible, so that if it’s implanted in a living body, pure elastin won’t trigger a rejection by the immune system. To Gregory, these attributes signify enormous potential for elastin and elastin-coated synthetics as a biomaterial.
“Mother Nature doesn’t use metal or plastic,” says Gregory. “We’re built of proteins, so I figured, why not do it the same way?”
As a cardiac surgeon, Gregory had experienced first-hand the limitations of metal and plastic replacement devices. Convinced that biomedicine is better off copying, or at the least seeking guidance from, Nature’s designs, he turned to elastin.
Several years ago, he began sending assistants on missions to a slaughterhouse to salvage discarded pig parts. Back at the lab, he separated and purified the elastin in it. Then his team identified the elastin-producing gene, enabling them to produce the protein using standard recombinant techniques.
After the elastin is made into sheets or tubes of tissue, a graft is implanted into an organism, at which point “cells move in,” according to Gregory, filling the spaces in between the elastin protein, which acts like a scaffolding. Gregory has found that blood vessel cells are populating the walls of the graft, while other potentially clotting cells so far are not appearing.
Gregory and his colleagues at the Oregon Medical Laser Center are pursuing research into medical uses for elastin with the aid of a $28 million grant from the Army. Last year, a surgeon at Tripler Army Medical Center in Hawaii, Chet Morrison, made incisions in the small intestines of 36 anesthetized pigs to investigate if they could be patched up with elastin.
Each wound was sewn up with a four-square-inch swatch of pure elastin from Gregory’s lab. All but one of the pigs survived (the one died from an unrelated cause) – and some were even eating normally the following day. Weeks later, when Morrison’s team opened up the pigs, some of the patches had been incorporated so completely into the organ tissue that they were difficult to locate. One researcher recalls that other doctors at the Center wished the patch was approved by the Food and Drug Administration, so they could use it on a patient who was suffering from a small-intestine tumor that required removal, prevented the patient from eating, and burdened him with a waste-collecting bag.
“We’re interested in ways to repair holes and other soft tissue injuries because, well, bullets make those kinds of holes,” says Morrison, who confirmed that human trials with the elastin patch are not far down the road.
As promising as these internal injury patches are, another potential market for elastin – vascular grafts – is much greater. They can be used to treat, among other medical problems, heart disease. An estimated 70,000 people a year cannot undergo invasive treatment for heart disease because their blood vessels are too small and fragile for a plastic stent (tubes used to hold open hollow structures within the body).
“The problem with current synthetics is that they have a high rate of clotting,” explains Raul Guzman, assistant professor of surgery at Vanderbilt University Medical Center.
What’s more, potential grafts from a patient’s own legs, arms, or chest are often too weakened themselves or have already been used in a previous surgery, leaving few options.
Despite its potential, though, pure elastin has limitations when used alone to make vessels. For one thing, it can tear easily, making suturing difficult, if not impossible. As a result, Gregory’s work now focuses on elastin “scaffolds” that incorporate a layer of stiffer protein (collagen) for structural integrity, grafts, and elastin-coated stents. If implant experiments using the stent on pigs prove successful this summer, Gregory hopes to gain approval for human clinical trials of stents in 2006.
In addition to the hundreds of thousands of bypass surgery patients who could benefit from the improved patching and support of valves, elastin research is aimed at helping soldiers who suffer injuries to their extremities – now one of the most common types of field casualties. Military surgeons would have a much better chance of saving a soldier’s hand or foot, for instance, if they could replace the smaller vessels that supply it with blood.
Finally, Gregory and his colleagues are hoping to literally grow vessels for patients. He’s an advisor to Honolulu-based Tissue Genesis Inc. (TGI), which is developing the mechanism to rapidly introduce populations of cells inside an elastin graft.
The idea, explains Gene Boland, TGI’s senior scientist for vascular tissue engineering, is to “harvest cells and rapidly put them on the inside of any conduit [vessel or a segment of a vessel] that we can then re-implant into the body. And we don’t need to go back to lab and grow it; we can do it all in the operating room.”
Vanderbilt’s Guzman describes the real-life case of a patient who would benefit from such improved vascular technology: a 69-year-old male with diabetes who had previously undergone a coronary artery bypass operation and two lower-extremity bypass procedures on his left leg.
“The first [bypass] was performed with PTFE [Gore-Tex] and the second [bypass]…with his own greater saphenous vein,” says Guzman, “Unfortunately, the vein graft clotted and he developed a non-healing ulcer on his foot. There were no suitable conduits available for revascularization and the patient subsequently underwent left leg amputation.”
When asked about the potential benefit for the kind of breakthrough technology that Gregory is pursuing, Guzman was unequivocal: “On a scale of 1 to 10, the value of solving this problem would be a 10.”
Portland, Oregon-based writer David Wolman reports on a variety of subjects, including health, energy, and oceanography. His first book, A Left-Hand Turn Around the World, about the science and culture of left-handedness, is due out this fall.